Glycodendrimer PPI as a Potential Drug in Chronic Lymphocytic Leukaemia. The Influence of Glycodendrimer on Apoptosis in In Vitro B-CLL Cells Defined by Microarrays

Title:Glycodendrimer PPI as a Potential Drug in Chronic Lymphocytic Leukaemia. The Influence of Glycodendrimer on Apoptosis in In Vitro B-CLL Cells Defined by Microarrays

Volume: 17 Issue: 1

Author(s): Ida Franiak-Pietryga, Ewelina Ziółkowska, Barbara Ziemba, Dietmar Appelhans, Henryk Maciejewski, Brigitte Voit, Aleksandra Kaczmarek, Tadeusz Robak, Barbara Klajnert-Maculewicz, Barbara Cebula-Obrzut, Piotr Smolewski, Maciej Borowiec and Maria Bryszewska

Affiliation:

Keywords: Apoptosis, chronic lymphocytic leukaemia (CLL), dendrimers, gene expression, glycodendrimers, poly(propylene imine) (PPI), protein expression, toxicity.

Abstract: Background: Chronic lymphocytic leukaemia (CLL) cells are characterized by failures in the apoptosis pathway and increased proliferation, resulting in the progressive accumulation of B-lymphocytes in blood. Despite the wide range of antileukaemic drugs, CLL remains an incurable disease. However, a breakthrough is expected which will allow more effective treatment.

Objective: The study investigates the influence of poly(propyleneimine) (PPI) dendrimer with peripheral amino groups, 30% of which were coated with maltotriose (PPI-G4-OS-Mal-III), on CLL cells, and demonstrates that it acts through the induction of the apoptotic mechanism. It is important to note that the dendrimer was used as a drug itself and not as a drug carrier.

Method: CLL and normal lymphocytes were treated in vitro with the dendrimer, either alone or in combination with fludarabine (FA). The percentages of apoptotic and necrotic cells, and the protein expression, were checked using a flow cytometer. Gene expression was screened using a two-colour microarray with 60-mer probes.

Results: The results confirm that PPI-G4-OS-Mal-III influences the viability of CLL cells in vitro and does not exert any significant harmful effect on normal lymphocytes. The dendrimer appears to significantly influence gene and protein expression in CLL cells.

Conclusion: Since dendrimers can be specifically targeted, they may be very effective in CLL therapy, especially since in vitro PPI-G4-OS-Mal-III has been found to have stronger effect than fludarabine.

Cite this article as:

Franiak-Pietryga Ida, Ziółkowska Ewelina, Ziemba Barbara, Appelhans Dietmar, Maciejewski Henryk, Voit Brigitte, Kaczmarek Aleksandra, Robak Tadeusz, Klajnert-Maculewicz Barbara, Cebula-Obrzut Barbara, Smolewski Piotr, Borowiec Maciej and Bryszewska Maria, Glycodendrimer PPI as a Potential Drug in Chronic Lymphocytic Leukaemia. The Influence of Glycodendrimer on Apoptosis in In Vitro B-CLL Cells Defined by Microarrays, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (1) . https://dx.doi.org/10.2174/1871520616666160622092947